crossing96/oncoscreening huggingface dataset:
Multiparametric MRI for assessing residual tumors in patients with muscle-invasive bladder cancer after neoadjuvant treatment: a reliable tool for guiding bladder preservation.	OBJECTIVE: To evaluate the clinical utility of multiparametric MRI in differentiating pathological stages (ypT0 vs ypT1-4) in patients with muscle-invasive bladder cancer (MIBCa) following neoadjuvant therapy (NAT). MATERIALS AND METHODS: In this double-center cohort study, post-NAT multiparametric MRI in all consecutive patients who underwent surgery after NAT was analyzed. Two experienced radiologists independently evaluated the MRI features obtained after NAT. The post-NAT yT stage was assigned based on T2-weighted diffusion-weighted imaging (T2DWI) and on contrast-enhanced MRI scans. The diagnostic accuracies for distinguishing post-NAT ypT0 from ypT1-4 tumors with the two protocols were evaluated. Cohen's kappa (κ) statistics were used to evaluate the consistency between readers for the post-NAT yT stage. RESULTS: A total of 149 patients (mean age, 62 years ± 10 [SD]; 131 men) from two institutions were enrolled. The area under the receiver operating characteristic curve of the contrast-enhanced MRI protocol in predicting post-NAT ypT0 stage was 0.84 (95% CI: 0.77, 0.91), which was better than that of the T2DWI protocol (0.75; 95% CI: 0.67, 0.81; p = 0.002). The interobserver agreement was excellent for both the T2DWI protocol (κ = 0.89) and the contrast-enhanced MRI protocol (κ = 0.85). CONCLUSIONS: Multiparametric MRI, particularly contrast-enhanced MRI, demonstrated superior accuracy in identifying ypT0 status following NAT in MIBCa, establishing it as an essential diagnostic tool for guiding bladder preservation in clinical decision-making. KEY POINTS: Question Accurately identifying pathological complete response (ypT0) after NAT is essential for selecting bladder-preservation strategies, yet remains clinically challenging. Findings Post-treatment contrast-enhanced MRI accurately identified ypT0 status with an AUC of 0.84 and excellent inter-reader agreement, outperforming T2DWI. Clinical relevance Contrast-enhanced MRI is a reliable, non-invasive method for detecting complete tumor response after NAT, enabling better patient selection for bladder-sparing approaches and potentially improving quality of life.	bladder
NR4A3 suppresses bladder cancer progression by modulating autophagy via the PI3K/AKT/mTOR pathway.	Bladder cancer (BC) is a prevalent and aggressive malignancy with high recurrence. Autophagy plays a dual role in cancer, acting as a tumor suppressor early on and promoting survival in later stages. NR4A3, a nuclear receptor with tumor-suppressive effects in other cancers, has not been explored in BC. NR4A3 expression was analyzed using TCGA data and validated in clinical BC samples via immunohistochemistry and RT-qPCR. NR4A3-overexpressing BC cell lines (5637, T24) were created using lentiviral vectors. Cell viability, proliferation, migration, and invasion were assessed through CCK-8, EdU, and Transwell assays. Autophagy was measured by microtubule-associated protein 1A/1B-light chain 3 (LC3), autophagy-related protein 5 (ATG5), Beclin-1 and p62 expression via immunofluorescence and Western blotting. The phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) / mammalian target of rapamycin (mTOR) pathway was examined by assessing phosphorylation levels. It was found that NR4A3 was significantly downregulated in BC tissues. Overexpression of NR4A3 inhibited BC cell proliferation, migration, and invasion, while promoting apoptosis. NR4A3 overexpression increased autophagy markers and suppressed PI3K/AKT/mTOR signaling. Autophagy inhibition reversed these effects. In conclusion, NR4A3 suppresses BC progression by promoting autophagy via the PI3K/AKT/mTOR pathway. Targeting NR4A3-mediated autophagy may provide a novel therapeutic strategy for BC.	bladder
The current and future role of systemic therapy in non-muscle-invasive bladder cancer.	Non-muscle-invasive bladder cancer (NMIBC) categorizes early-stage urothelial carcinoma that has not invaded the bladder's muscle layer. Although it is initially treatable with transurethral resection, NMIBC has a high risk of recurrence and progression, which necessitates prolonged surveillance and intravesical therapies. Intravesical bacillus Calmette-Guérin (BCG), originally developed as a tuberculosis vaccine, has proven effective in reducing recurrence and delaying progression in NMIBC. Notably, BCG immunotherapy was among the first treatments to demonstrate that activating the immune system could control localized urothelial cancer. Although there has been recent growth in novel intravesical therapies for patients with BCG-unresponsive disease, options remain limited, and radical cystectomy is still frequently performed. Recent advances in systemic therapies, especially immunotherapies targeting the programmed cell death protein 1/programmed death ligand 1 pathway, have now affected NMIBC, with pembrolizumab receiving regulatory approval. This development has spurred numerous clinical trials investigating systemic therapeutic agents in NMIBC alone or in combination with other modalities such as intravesical therapy or radiation to improve outcomes. To understand the current landscape in this clinical space, a systematic review of systemic therapy in NMIBC was performed. Current data and ongoing studies that use systemic agents to treat this disease are presented. Despite recent progress in this domain, there remains a substantial need for more effective treatments with fewer toxicities for NMIBC. Future trials will be essential for optimizing these therapies and improving patient outcomes.	bladder
Risk factors of severe prolonged hypotension induced by 5-aminolevulinic acid during photodynamic diagnosis-assisted transurethral resection of bladder tumor.	BACKGROUND: To identify the risk factors of severe prolonged hypotension induced by 5-aminolevulinic acid (ALA) for non-muscle invasive bladder cancer patients undergoing photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumor (TURBT). METHODS: We retrospectively performed multivariate analyses to identify the clinical risk factors for ALA-induced severe prolonged hypotension, defined as requiring: (1) prolonged vasopressor treatment, (2) frequent treatment with vasopressor, and (3) continuous noradrenaline administration (systolic blood pressure < 80 mmHg) in bladder cancer patients undergoing PDD-TURBT. RESULTS: A total of 245 patients who underwent PDD-TURBT were included in the final analysis. Risk factors (p < 0.05) by multivariate analyses were high body mass index, concomitant atrial fibrillation, low estimated glomerular filtration rate and short ALA exposure time. Predisposing risk factors (0.05 ≤ p < 0.2) on multivariate analysis included concomitant hypertension and use of calcium channel blockers. Analyses of the effect of combination of the four risk factors on the duration of vasopressor treatment showed patients with two or three risk factors significantly more frequently received vasopressor treatment for a duration of ≥ 60 min than those without risk factors (p < 0.05). CONCLUSIONS: We identified independent risk factors and combinations of multiple factors related to ALA-induced severe prolonged hypotension in bladder cancer patients undergoing PDD-TURBT. In patients with multiple risk factors, it is advisable to maintain a longer interval between ALA administration and anesthesia to avoid severe prolonged hypotension.	bladder
TET3 facilitates bladder cancer progression through targeted modulation of stemness pathways.	Bladder cancer is a major health concern, and understanding its molecular mechanisms is essential for developing effective therapies. TET3, a DNA hydroxymethylase, has been linked to tumor progression, but its role in bladder cancer remains unclear. We analyzed single-cell RNA sequencing data and identified TET3 as a key regulator in tumor-promoting cells using scissor analysis. Functional experiments were performed to evaluate the effects of TET3 knockdown on cell proliferation, migration, and gene expression. In vivo tumor growth assays and histological analyses were conducted to assess the role of TET3 in tumor progression. Additionally, we assessed the impact of TET3 on stemness-associated gene expression and performed sphere formation assays to evaluate tumor cell self-renewal capacity. TET3 was highly expressed in tumor-promoting cells. Its knockdown significantly reduced cell proliferation, migration, and tumor growth in vivo. Tumors with TET3 knockdown had lower volumes, weights, and Ki67-positive cells. Mechanistically, TET3 regulated key tumor-related genes and pathways and reduced DNA 5hmC levels. Notably, TET3 knockdown downregulated multiple stemness-related transcription factors such as SOX2 and NANOG, and impaired sphere-forming efficiency, suggesting its essential role in maintaining cancer cell stemness. This study reveals that TET3 promotes tumor growth and progression in bladder cancer partly through modulation of the stemness pathway, highlighting its potential as a therapeutic target and prognostic marker.	bladder
Use of Rectal Diazepam to Prevent Bladder Spasms and Leakage of Medication During Intravesical Administration of Nadofaragene Firadenovec for Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer.	PURPOSE: Nadofaragene firadenovec-vncg is a US Food and Drug Administration-approved therapy for bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer. Bladder spasms and medication leakage during intravesical instillation are common and can affect treatment efficacy. We evaluated the effect of rectal diazepam pretreatment on bladder spasm incidence, retention of instilled medication, and 3-month recurrence rates. MATERIALS AND METHODS: We retrospectively analyzed data from patients treated with nadofaragene firadenovec for bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer at Mayo Clinic from November 28, 2023, through September 30, 2024. Patients were stratified by pretreatment with rectal diazepam (10 mg) vs other strategies. Outcomes included bladder spasms, retention of instilled medication, and 3-month recurrence rates. RESULTS: Eighty-eight nadofaragene firadenovec instillations (45 patients) were evaluated. Rectal diazepam pretreatment was used for 25 instillations (28%) and associated with a 25% absolute risk reduction for nadofaragene firadenovec retention failure (4.0% vs 29% of instillations), as compared with other pretreatments (patient-level odds ratio, 0.22 [95% CI, 0.11-0.44]; P < .001). In addition, we observed a 24% absolute reduction in bladder spasm incidence (32% vs 56% of instillations) in the rectal diazepam group (patient-level odds ratio, 0.32 [95% CI, 0.13-0.82]; P = .02). Patients without medication leakage had a lower recurrence rate at 3 months (18% vs 38%), although this difference was not statistically significant (P = .3). One patient had fatigue attributable to rectal diazepam. CONCLUSIONS: Rectal diazepam pretreatment may reduce bladder spasms and improve nadofaragene firadenovec retention during intravesical instillation, thereby enhancing efficacy. Rectal diazepam could improve patient comfort and treatment outcomes, thus warranting further investigation through larger, prospective studies.	bladder
KIAA1429 and AlkB Homolog 5 Regulate Bladder Cancer Progression via N(6)-Methyladenosine-Dependent Modulation of Sonic Hedgehog Signaling.	N(6)-methyladenosine (m(6)A) modification plays a pivotal role in cancer progression, yet its regulatory mechanisms in bladder cancer (BCa) remain poorly understood. This study investigates the functions of two key m(6)A regulators-α-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5) and KIAA1429-in modulating BCa cell behavior. Expression levels of ALKBH5, KIAA1429, and Sonic Hedgehog (SHH) were examined in BCa tissues and adjacent normal tissues. Functional assays, including methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR), RNA immunoprecipitation (RIP), and RNA stability assessments, were performed in J82 BCa cells to explore the underlying mechanisms. Results revealed that KIAA1429 was significantly upregulated in BCa and promoted cell proliferation, migration, and invasion by enhancing m(6)A modification and stabilizing SHH mRNA, leading to activation of the Hedgehog signaling pathway. In contrast, ALKBH5, which was downregulated in BCa, acted as an m(6)A demethylase that destabilized SHH mRNA and attenuated Hedgehog pathway activity, thereby counteracting the oncogenic effects of KIAA1429. Moreover, overexpression of SHH reversed the inhibitory effects induced by KIAA1429 knockdown, confirming its role as a downstream effector. In conclusion, ALKBH5 and KIAA1429 exert opposing regulatory effects on BCa progression via m(6)A-mediated modulation of SHH expression and Hedgehog signaling. These findings highlight SHH mRNA methylation as a central mechanism in BCa malignancy and identify ALKBH5 and KIAA1429 as potential therapeutic targets.	bladder
What spatial omics is teaching us about field cancerisation in prostate and bladder cancer.	BACKGROUND AND OBJECTIVES: Field cancerisation is the process that results in a group of cells acquiring some of the phenotypic changes of cancer prior to transformation into cancer. Clinically, an important challenge remains the ability to distinguish clonal lineages and microenvironments within cancerised fields that will remain indolent from those that will progress to malignant transformation. Spatial 'omics' can help us investigate genetic, epigenetic, transcriptomic, proteomic, and cellular microenvironments that transform normal cells into a cancerised field, and subsequently into cancer. In this review, we will discuss how spatial omics techniques have expanded our understanding of field cancerisation in prostate and bladder cancer, and the challenges associated with this research. METHODS: We identified key articles relating to field cancerisation in bladder and prostate cancer. Special emphasis was placed on studies that used modern spatial profiling technologies and studies that were designed to investigate changes within normal tissue rather than simply using it as a control for tumour tissue. RESULTS: Spatial omics research into field cancerisation has identified interesting early findings that have informed our understanding of: transformation of the benign epithelium and mechanisms of intra-prostatic clonal expansion for prostate cancer; clonal expansion within the normal urothelium; mutations that are unique to cancerised fields within the bladder; and how field cancerisation may prime the urothelium for cancer transformation. CONCLUSIONS: Spatial omics profiling of field cancerisation can inform risk stratification and personalised treatment options. However, there are a number of challenges associated with the technologies that must be overcome before the potential of spatial omics can be fully realised in clinical practice.	bladder
Association between CYP17A1 rs743572 polymorphism and cancer risk: A meta-analysis.	The role of the CYP17A1 gene's rs743572 polymorphism in cancer susceptibility has been a subject of extensive investigation, yet existing evidence remains inconclusive. In this meta-analysis, we systematically reviewed and synthesized data from 29 studies to assess the CYP17A1 rs743572 polymorphism's relationship with cancer susceptibility. We strictly searched on EMBASE, PubMed, and Web of Science databases and explored rs743572 polymorphism's association with cancer risks according to search strategy, enrolling 29 studies (13,767 cases and 17,441 controls). rs743572 was markedly related to enhanced cancer susceptibility risk; FPRP and TSA analyses were employed for confirmation. According to cancer type-based stratified analyses, rs743572 exhibited a notable association with bladder cancer, breast cancer, non-Hodgkin lymphoma, and hepatocellular cancer. In conclusion, systematic meta-analysis suggests a significant role for the rs743572 polymorphism in cancer pathogenesis, with particular prominence observed in bladder cancer, breast cancer, non-Hodgkin lymphoma, and hepatocellular cancer.	bladder
Preoperative prediction of severe short-term complications in patients with bladder cancer undergoing radical cystectomy.	BACKGROUND AND OBJECTIVE: Radical cystectomy (RC) is associated with a high risk of postoperative complications. The prediction of individual patient risk for severe complications can facilitate preoperative shared decision-making. Patients with elevated risk may be referred to prehabilitation with the aim to mitigate the risk to improve perioperative outcomes. We developed models to predict severe short-term postoperative complications using preoperatively available clinical variables. METHODS: Data from a prospective cohort of 1313 RC patients treated between 1999 and 2021 was used. Preoperative demographic, laboratory, and cancer-related variables were defined as domains to predict severe complications measured by the Comprehensive Complication Index (CCI). Machine-learning models were trained for each postoperative day and predictor domain. The area under the receiver operating characteristic curve (AUROC) was reported as the primary outcome. Clinical utility was examined using Decision Curve Analysis (DCA). RESULTS: The best performing model had an AUROC of 0.69 (95 % CI 0.63-0.75) for severe complications on postoperative day (POD) 14. Mean AUROCs across POD 1-30 were 0.64 for all variables combined, 0.58 for demographics, 0.56 for laboratory values, and 0.53 for cancer-related factors. Model calibration and stability improved from POD 10 onwards. Decision curve analysis indicated the highest net benefit from models incorporating all predictors, with demographic variables contributing most among individual domains. CONCLUSIONS AND CLINICAL IMPLICATIONS: Limited clinical utility of the trained models was observed. The benefit for preoperative clinical decision-making is unclear. Clinical utility may improve by the inclusion of variables related to function in future models (e.g., frailty).	bladder
LncRNA TRPM2-AS promotes cell proliferation, migration, and invasion by regulating the miR-195-5p/COP1 axis in bladder cancer.	Bladder cancer (BLCA) is one of the most frequent malignant tumors worldwide, with markedly poor prognosis when distant metastasis occurs. Long noncoding RNA (lncRNA) TRPM2-AS has been reported to play an oncogenic role in several cancers. Although TRPM2-AS was previously revealed to suppress BLCA cell growth, its role in BLCA cell metastasis remains largely unknown. In our study, TRPM2-AS, miR-195-5p, and COP1 relative expression in BLCA cells was estimated by RT-qPCR. Through MTT, EdU, colony formation, wound-healing, Transwell, and western blotting assays, the biological effects of TRPM2-AS and COP1 on BLCA cell proliferation, migration, invasion, and EMT were evaluated. Target association between miR-195-5p and TRPM2-AS (or COP1) was confirmed by RNA pull-down, RIP, and luciferase activity assays. The nucleocytoplasmic localization of TRPM2-AS in BLCA cells was measured by FISH assay. Xenograft mouse models of BLCA were used to validate the role of TRPM2-AS on tumor growth and EMT in vivo. Our results showed that TRPM2-AS and COP1 expression was increased, while miR-195-5p expression was decreased in BLCA cells and tissues. TRPM2-AS silencing repressed BLCA cell growth, migration, invasion, and EMT. TRPM2-AS acted as a competing endogenous RNA (ceRNA) to spongemiR-195-5p, thereby positively regulating COP1 expression and activating the PI3K/AKT signaling. Overexpressing COP1 antagonized the influence of TRPM2-AS knockdown on BLCA cell growth, migration, invasion, and EMT. Additionally, TRPM2-AS knockdown inhibited tumor growth, EMT, and the PI3K/AKT signaling, attenuated COP1 expression, and enhanced miR-195-5p expression in xenograftmouse models. Collectively, TRPM2-AS functions as an oncogene in BLCA development via the miR-195-5p/COP1 axis.	bladder
Re-appraisal of Standard of Care Imaging to Identify Predictors of Treatment Outcomes among Patients with Bladder and Upper Tract Urothelial Cancers.	PURPOSE OF REVIEW: Urothelial carcinoma is a prevalent malignancy within the United States that may involve the upper and/or lower urinary tracts. Multimodal treatment is often employed, with transurethral resection and intravesical therapy standard of care for non-muscle-invasive disease; neoadjuvant systemic therapy followed by radical cystectomy or trimodal therapy for muscle-invasive disease; and combination immune checkpoint inhibitors and antibody-drug conjugates standard of care for metastatic disease. These treatments carry risks of surgical complication or treatment-associated toxicity which can impair quality of life. Predictive biomarkers of treatment tolerability are currently limited. RECENT FINDINGS: There is emerging evidence that radiological biomarkers can predict treatment outcomes among patients with urothelial carcinoma. In this review, we evaluate the existing data on radiological biomarkers evaluable from current standard-of-care imaging in predicting treatment outcome among patients with urothelial carcinoma.	bladder
TFAP2C drives cisplatin resistance in bladder cancer by upregulating YAP and activating β-catenin signaling.	Cisplatin-based chemotherapy is a conventional therapy for muscle-invasive bladder cancer (BC); however, its efficacy is often limited by the emergence of resistance to cisplatin. Yes-associated protein (YAP) and β-catenin are involved in this resistance, yet their upstream regulators are not well defined. This study investigates the role of TFAP2C in regulating YAP expression and its impact on cisplatin resistance in BC. The Cancer Genome Atlas (TCGA) gene expression data and GSE231835 dataset were analyzed to identify potential transcription factors regulating YAP. Assessed TFAP2C and YAP expression in clinical samples and cell lines. Functional assays were performed following TFAP2C knockdown. Dual-luciferase reporter assays and Chromatin immunoprecipitation (ChIP) confirmed TFAP2C binding to the YAP promoter. A mouse model evaluated the effects of TFAP2C silencing on tumor growth and cisplatin resistance. The results showed that TFAP2C was identified as an upstream activator of YAP, with elevated expression in cisplatin-resistant BC cell lines and positive correlation with YAP expression. Silencing TFAP2C reduced malignant behaviors, decreased YAP, phosphorylated YAP (p-YAP) and β-catenin levels, and increased apoptosis in both cisplatin-sensitive and cisplatin-resistant BC cells. Besides, TFAP2C directly binds to the YAP promoter, enhancing its transcription. In the xenograft model, TFAP2C silencing significantly inhibited tumor growth and reduced cisplatin resistance. TFAP2C promotes cisplatin resistance and malignant behavior in BC by upregulating YAP and activating the β-catenin signaling pathway. Targeting TFAP2C offers a novel therapeutic strategy to overcome cisplatin resistance in BC, representing a new discovery in combating chemoresistance.	bladder